Bacterial and Viral STIs and Their Sequelae
Both bacterial and viral STIs are widespread in developing countries; recently, incidence of bacterial STIs has declined while that of viral STIs has been increasing.
Natural History of Bacterial STIs and Their Sequelae
Chancroid is a genital ulcer disease caused by Haemophilus ducreyi. Its incidence has declined greatly in both developed and developing countries. This decline has been associated with the provision of STI diagnostic and therapeutic services to sex workers (Steen 2001) and with improved syndromic management of genital ulcers. Like other genital ulcer diseases, chancroid is associated with increased acquisition and transmission of HIV (Donovan 2004).
Syphilis is a genital ulcer disease caused by Treponema pallidum. In 1999, the World Health Organization (WHO) estimated the global prevalence of syphilis at 12 million (WHO 2001a), with high prevalence rates in South and Southeast Asia and Sub-Saharan Africa. Those most likely to be affected are populations in developing countries and disadvantaged sub-populations in developed countries. Since 1999, syphilis outbreaks have reemerged in many developed countries among men who have sex with men (CDC 2004; L. Doherty and others 2002). Among heterosexuals, sexual contact with sex workers is an important risk factor. If untreated, syphilis during pregnancy may lead to stillbirth and congenital syphilis (Genc and Ledger 2000).
Gonorrhea is a discharge disease caused by N. gonorrhoeae. In 1999, WHO estimated its global prevalence at 62.4 million (WHO 2001a). Like syphilis, its prevalence is high in South and Southeast Asia and Sub-Saharan Africa, in many developing countries elsewhere, and among high-risk groups and disadvantaged subpopulations in developed countries. Community surveys reveal a substantial pool of asymptomatic gonococcal infections (Chandeying and others 2000; Turner and others 2002). Following the emergence of AIDS, gonorrhea cases declined among men having sex with men, sex workers, and the general population in the developed world and among sex workers in many developing countries (Donovan 2004).
In most populations tested, infection with Chlamydia trachomatis is the most common bacterial STI. In 1999, WHO estimated the global prevalence of chlamydial infection to be 92 million (WHO 2001a). Chlamydial infection is common in most countries, especially among young people. Key risk factors are being younger than 25 and having a new sex partner. Many women with uncomplicated infection are asymptomatic or have mild symptoms. Like untreated gonococcal infection, untreated chlamydial infection can cause pelvic inflammatory disease, chronic pelvic pain, and ectopic pregnancy. Chlamydial infection is an important acquired cause of infertility in women (Simms and Stephenson 2000). Roughly half of men with urethral chlamydial infection develop symptomatic urethritis, chlamydial infection is the most common cause of epididymitis in young men, and both men and women may develop chlamydial conjunctivitis or reactive arthritis (Stamm 1999). Research also suggests that chlamydial infection in men may be associated with reduced fecundity among couples (Idahl and others 2004). In addition, chlamydial infection can affect neonates: many delivered vaginally become infected, developing conjunctivitis or, less often, chlamydia pneumonia (Donovan 2004). The role of C. trachomatis in preterm births and in cervical cancer awaits further clarification through research (Samoff and others 2004; Wallin and others 2002).
In the absence of control programs, the prevalence of Trichomonas vaginalis varies greatly across countries, ranging from less than 1 percent among urban women to more than 20 percent in underserved populations in the same country (Brown and Brown 2000), and may increase with age. WHO estimated the global prevalence of T. vaginalis at 174 million in 1999. The introduction of nucleic acid amplification tests highlighted the poor sensitivity of microscopy in the detection of T. vaginalis. Even though most infected people are asymptomatic, T. vaginalis can cause vaginitis with vaginal discharge in women and urethritis in men. T. vaginalis has been associated with preterm birth and may promote the sexual transmission of HIV (Laga and others 1993). However, a randomized controlled trial did not show that screening and treatment for T. vaginalis to prevent preterm birth were effective (Klebanoff and others 2001).
Like T. vaginalis, bacterial vaginosis and vulvovaginal candidiasis cause vaginal symptoms in women, are extremely prevalent in developing countries, and in one or more studies have been associated with HIV acquisition or HIV genital shedding by women (Donovan 2004). Although often referred to as reproductive tract infections rather than STIs, they are managed in conjunction with STIs, and bacterial vaginosis is associated with some of the same risk factors as other STIs.
Viral STIs and Their Sequelae
Both HSV-1 and HSV-2 infect the genital and anal areas, but HSV-2 causes the most clinical recurrences in the genital tract. Symptoms are mild in most of those infected and tend to go unrecognized and undiagnosed (Corey 2000; Scoular 2002). Genital herpes establishes a lifelong infection that in some people is associated with significant morbidity. Complications of HSV-2 include severe primary disease, meningitis, hepatitis, erythema multiforme, and neonatal herpes (Donovan 2004). Infected neonates may die or develop severe neurological sequelae despite antiviral therapy. In contrast to bacterial STIs, HSV-2 may be transmitted to sex partners many years after initial infection and during periods when the infected individual may be asymptomatic. Infection with HSV-2 is now one of the most common STIs worldwide and is the most frequent cause of genital ulcers in almost all areas; however, this observation may be related to better diagnostic technologies rather than a genuine alteration in the spectrum of genital ulcer disease (Corey and Handsfield 2000). Improved control of chancroid and syphilis as well as actual increases in the sexual transmission of HSV-2 in areas with advanced HIV epidemics, where HIV-related immunosuppression causes more frequent and more severe HSV-2 disease, may also play a role. Estimates indicate that 10 to 30 percent of adults worldwide are infected with HSV-2 (Brugha and others 1997). Prevalence increases with age and is higher in women and high-risk populations.
HPV types are grouped into low-risk (nononcogenic) and high-risk (oncogenic) types. Low-risk types, including types 6 and 11, cause benign anogenital warts, whereas high-risk types, including HPV 16, 18, 31, and 45, occasionally lead to genital and anal squamous cell cancers. The introduction of nucleic acid amplification tests revealed that genital and anal HPV infection is common even among relatively sexually inexperienced individuals (Giuliano and others 2002; Stone and others 2002). Investigators believe that most adults become infected with HPV but that only a few develop warts or genital or anal cancer. Infection with a high-risk HPV type is implicated in nearly all cases of invasive cervical cancer (Walboomers and others 1999) and with vaginal, vulvar, and anal cancers.
In developed countries, hepatitis B virus is spread predominantly by sexual and injecting drug-use transmission. Indeed, the first three trials of hepatitis B vaccine successfully demonstrated prevention of sexual transmission of hepatitis B virus in men who have sex with men (Manhart and Holmes 2005). In developing countries, hepatitis B is more often acquired perinatally or during childhood, but a rise in seroincidence in adolescence and young adulthood in some countries probably reflects sexual or injecting drug-use transmission. Hepatitis B virus causes acute hepatitis and in some people causes chronic hepatitis that can lead to cirrhosis and liver cancer.
Human T cell lymphotropic virus type I (and perhaps in more cases type II) is, like hepatitis B virus, transmitted perinatally and sexually. In some high-risk populations, for example, female sex workers in Latin America, human T cell lymphotropic virus type I infection is substantially more common than HIV infection. This infection causes a serious form of spastic paralysis or human T cell lymphotropic-associated myelopathy, as well as T cell lymphoma or leukemia.
Coinfection with Sexually Transmitted Pathogens
The epidemiology and natural history of coinfection with more than one sexually transmitted pathogen may have important intervention and economic implications. Coverage by clinical services, outreach, access, partner management, and treatment may be different with coinfection than with independent infections. Although coinfections with HIV and other STIs have received a great deal of attention in recent years, researchers have not focused on overlaps among non-HIV STIs in a similar systematic manner. A number of biological mechanisms may lead to coinfection with STIs: infection with one pathogen may increase the probability of acquiring or transmitting another pathogen; infection with one pathogen may increase or decrease the frequency, the severity, or both of symptoms associated with another sexually transmitted pathogen; and presence of one STI may affect the natural history of another STI. High-risk behaviors and networks often lead to coinfection.
Empirical data on coinfection are limited. Most studies have been conducted in developed countries and have focused on co-occurrences of chlamydial and gonococcal infection. Earlier studies of coinfection assessed the proportion of gonorrhea cases with concurrent chlamydial infection in a variety of clinical settings. Reported levels of coinfection were 4 to 64 percent among attendees at STI clinics, 46 percent among prenatal clinic attendees, and 4 to 25 percent at primary health care facilities (Creighton and others 2003). The proportion of those with chlamydia who also have gonorrhea has been assessed less well, and estimates have ranged between 3 and 4 percent (Creighton and others 2003).
Sexual Behavior and Sexual Health Care
Unprotected sex with an infected partner is the most important risk factor for acquiring an STI. This risk is influenced by the behaviors of the individual and the probability that the partner is infected, which is determined by the prevalence and distribution of infection in the population as well as the partner's behaviors. Current approaches to STI epidemiology recognize at least three distinct components of transmission dynamics at the population level: likelihood of sexual exposure between infected and uninfected individuals, transmissibility of infection upon exposure between an infected and an uninfected person, and duration of infection among those infected (Aral and Holmes 1999; Over and Piot 1993). The first of these components is entirely behavioral, and behavior plays an important role in the last two—for example, condom use, sexual practices, and health care-seeking behaviors.
Demographic and Social Risk Markers
The prevalence and incidence of STIs vary across societies and subpopulations defined by age, gender, race and ethnicity, and socioeconomic status (Fenton, Johnson, and Nicoll 1997). In all societies, adolescents and young people are at greater risk for acquiring most STIs. Women tend to have a higher prevalence and incidence of all STIs (except for men who have sex with men) and suffer more of the serious complications, such as pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic abdominal pain. For many STIs, the probability of transmission from an infected man to a susceptible woman is higher than from an infected woman to a susceptible man. Social and behavioral patterns also increase women's vulnerability to STIs; for instance, many men have concurrent sex partnerships, which increase their risk for transmitting infection to their female sex partners. In addition, many young women have sex with older male partners, who expose them to the higher STI prevalence rates in older age groups.
In most societies, minority racial ethnic groups have higher STI rates than other groups. Both in the United Kingdom (Fenton, Johnson, and Nicoll 1997) and in the United States (Laumann and Youm 1999), assortative sexual mixing and higher rates of sexual mixing with members of core groups emerge as determinants of ethnicity differentials in STI rates. The prevalence of concurrent partnerships is also higher among racial ethnic minorities (Kraut-Becher and Aral 2003). The relative inadequacy of STI health services and of health care-seeking behaviors among minority racial ethnic groups may also contribute to their higher prevalence of STIs (Aral and Wasserheit 1999).
Socioeconomic status differentials in STI prevalence and incidence are similar to ethnicity differentials. However, the multicollinearity between the two factors makes delineating the independent contributions of either variable to differentials in STI prevalence and incidence difficult.
Behavioral Risk Factors for Exposure to Infected Sex Partners
Most sexual behaviors of individuals are associated with exposure to sex partners infected with sexually transmitted pathogens and, consequently, with acquisition of STI. These behavioral factors include number of sex partners over the individual's lifetime, over the past year, and over a short term (Fenton and others 2001; Laumann and Youm 1999); frequency or number of sexual encounters (Garnett and Rottingen 2001); having sex with members of groups with high STI prevalence, such as core groups and sex workers (Fenton and others 2001; Laumann and Youm 1999) or older age groups (Service and Blower 1996); and position in a sexual network (I. A. Doherty and others 2005). Some sexual behaviors of individuals are associated with transmission of STIs, and for those infected the behaviors increase the probability that people will transmit their infections to susceptible sex partners. These behaviors include having concurrent partnerships (Koumans and others 2001; Kraut-Becher and Aral 2003; Morris and Kretzchmar 1995) and having short gaps between sex partners in serial monogamous partnerships (Kraut-Becher and Aral 2003).
Sex partners' behaviors are also critical determinants of exposure to infection. Investigators use many behavioral and epidemiological indicators to assess partners' risk of having infection, including existence and number of new sex partners; presence of concurrent partnerships; gap between sex partners; partners' number of partners; and risk status of partners' partners—for example, if they have sex with sex workers or men who have sex with men (Aral 2002b).
Behavioral Risk Factors Associated with STI Acquisition and Transmission on Exposure to Infected Partners
Certain behaviors influence the likelihood of an infected person's transmitting infection to a susceptible partner, including condom use, sexual practices such as anal intercourse, vaginal douching, and use of drying agents in the vagina (Bailey, Plummer, and Moses 2001; Donovan 2000a; Donovan 2000b). The probability of transmission varies depending on the pathogen and is much higher for bacterial STIs, such as gonorrhea, syphilis, and chlamydia, than for other STIs, such as HIV infection. Thus, preventive behaviors such as condom use may be more effective in preventing the latter than the former (National Institute for Allergy and Infectious Diseases 2001). In addition, the probability of both acquisition and transmission is significantly affected by such nonbehavioral cofactors as circumcision status (Aral and Holmes 1999).
Overall, oral sex and anal sex tend to be practiced less often in the developing world than in the developed world (Vos 1994). Insertion of herbs to tighten or dry the vagina and other practices of vaginal clearing and wiping are widespread (Brown and Brown 2000). Condom use is increasing in some countries—for example, India, Thailand, and Uganda—especially during high-risk encounters.
Behaviors Associated with the Duration of Infectiousness
The duration of infectiousness is an important component of transmission dynamics. Because effective treatment curtails the duration of curable STIs, the speed with which infected individuals seek treatment and the speed and effectiveness with which health care providers supply effective treatment together determine duration. To the extent that suppressive therapies truncate the period of infectiousness of viral STIs, as they do for HSV-2 and HIV infection, duration is also important in the transmission dynamics of incurable viral STIs.
Behaviors that can reduce the average duration of infectiousness include timely and appropriate health care seeking, effective participation in risk assessment, and compliance with therapy and prevention recommendations on the part of those infected and at risk (Aral and Wasserheit 1999). Health care seeking depends on perceived seriousness and causality of symptoms, availability and accessibility of health care, costs (including opportunity costs) of treatment, perceived and actual quality of care, and beliefs about the appropriate provider to consult. The proportion of those infected seeking care is highly variable, and delays in seeking treatment can be substantial. In many places, the proportion of people seeking timely care from appropriately trained providers is limited (Hawkes and Santhya 2002; Moses and others 2002; Rekart 2002).
Behaviors on the part of health care providers that ensure timely and accurate diagnosis, appropriate treatment, and non-judgmental attitudes toward those infected would also help reduce the duration of infectiousness of STIs. However, establishing effective, accessible, affordable, and decentralized services is difficult (Over 2004; World Bank 2003). The major barriers Moses and others (2002) identified in Nairobi reflect the situation in many developing countries. Those barriers include inadequate basic training and inefficient deployment of health workers; attitudes of health workers toward marginalized groups (for instance, female sex workers); high patient loads at health centers; lack of supportive supervision; inadequate referral systems; chronic shortages of supplies and drugs; and inadequate recording of health information. User fees can be a substantial additional barrier, though they may contribute to the sustainability of the treatment program and improve the provider's incentives.
Behavioral Interactions
Both at the individual and the population levels, people's risk behaviors respond to changing circumstances. In many developing countries where HIV incidence has been high, people have adopted compensatory behavior changes, such as delayed age of sexual debut, reduced number of sex partners, and increased use of condoms (Shelton and others 2004; Stoneburner and Low-Beer 2004), especially with high-risk partners (Peterman and others 2000). Some people now seek health care when they suspect they have been exposed to an STI.
At the same time, risk behaviors can overlap: people who initiate sexual activity early in life tend to have many partners, and people who engage in risky sex tend to also use drugs and alcohol. A history of sexual abuse or of being an abuser is also positively associated with high-risk sexual behaviors and drug use (Aral 2004). The adoption of preventive behaviors raises the possibility that people will compensate by changing other behaviors in response; for example, many believe that the widespread adoption of antiviral therapy or condom use may lead to increases in the numbers of sex partners (Blower and others 2001; Blower and Farmer 2003; Over and others 2004). Although constructing mathematical models to explore the effects of such changes in behavior is helpful, empirical research in varied contexts is urgently needed to identify the variables that determine patterns of interaction among risky and preventive behaviors. Two such variables may be individual autonomy and awareness of the epidemiological context.
Societal Determinants of STIs
Sexual networks and patterns of sexual partnership formation and dissolution constitute a major mechanism through which the political economy and the sociolegal system influence the rate of spread of STIs in a population. Sexual networks that are highly critical to the rate of spread of STIs include those involving sex work; exchange of sex for drugs, gifts, or material needs; and anonymous sex. The frequency of sex in exchange for money or other goods appears to be highly sensitive to changes in the political economy and the sociolegal system. Internal conflicts, war, economic crises, and social collapse are accompanied by the establishment of major sex markets or the expansion of existing ones. For example, following the collapse of the former Soviet Union, the number and size of commercial sex and sex-drug networks expanded significantly (Aral and St. Lawrence 2002; Aral and others 2005). The availability and use of condoms also influence the rate of spread of STIs.
Many developing countries continuously face political conflict, war, economic deterioration, mass migration, and increasing inequality plus the effect of globalization. In addition, in most developing societies, gender power relationships are marked by great inequality. Those contextual factors lead to sexual networks and sexual mixing patterns that are highly conducive to the spread of STIs. Sexual partnerships are often not stable, and in the long-term absence of a spouse, both men and women (but especially men) have other partners.
In addition, as economic needs rise, the number of women who exchange sex for material needs increases. Wilson and others (1989) estimate that approximately 10 percent of the female population in Bulawayo, Zimbabwe, had engaged in full- or part-time sex work at some time in their lives, whereas Aral and St. Lawrence's (2002) estimates for Saratov, Russian Federation, are closer to 25 percent. As the supply of sex workers increases, the demand for their services often increases in parallel. Economic need also affects sexual mixing patterns. In most developing countries, young girls commonly have "sugar daddies"—that is, older, often married men who provide them with material goods in return for sex while also exposing them to chronic STIs typical of relatively older cohorts (Gregson and others 2002).
Gender inequalities put women in a highly vulnerable position in many ways. For example, Decosas and Padian (2002) find that, among women attending family-planning and primary health care clinics in Zimbabwe, 17 percent had at some time received a gift in exchange for sex, 22 percent had been forced to have sex with a steady partner, 5 percent had been forced to have sex with a nonsteady partner, 35 percent were certain their steady partner had other partners, 27 percent said their partners had STI symptoms, 24 percent said their partner was intoxicated during sexual intercourse more than half the time, and only 10 percent had used a condom in the previous three months.
Income and Inequality
A cross-country database (George Schmid, personal communication, September 15, 2004) enables us to analyze the association between national STI prevalence rates and two important economic variables: gross national income per capita and the degree of income inequality as measured by the Gini coefficient.1 As table 17.1 shows, these two variables explain 45 percent of the variation in STI prevalence in low-risk groups and 16 percent of STI prevalence in high-risk groups. Figure 17.1 illustrates the relationship between each of these two economic variables and STI prevalence.
[Figure
17.1]
[Table .]
Poor countries' higher prevalence rates of STIs are unsurprising and could be explained by the fact that people in richer countries are likely to seek and find care for STIs more quickly. More notable is that income inequality is such a strong predictor of STI prevalence even after controlling for gross national income per capita. Furthermore, income inequality is a strong predictor of STI prevalence among high-risk groups, where income per capita performs less well. A possible explanation for this finding is that greater inequality creates more active markets for commercial and casual sex as higher-income men negotiate for the sexual services of lower-income sex workers (Aral 2002b; Over 1998).
